TNF-α单克隆抗体对梗阻性黄疸大鼠肾脏保护作用的实验研究

Experimental Study about the Protective Effect of Anti-TNF-α Mcab on Kidney of Rats with Obstructive Jaundice

目的研究肿瘤坏死因子-α(TNF-α)在梗阻性黄疸大鼠肾损伤中的作用及抗肿瘤坏死因子-α单克隆抗体(anti-TNF-αMcAb)的保护作用。方法将雄性SD大鼠24只随机分为胆总管结扎组(BDL)、胆总管结扎+抗肿瘤坏死因子-α单克隆抗体治疗组(BDL+anti-TNF-αMcAb)、假手术组(SO)。BDL组和BDL+anti-TNF-αMcAb组均作胆总管结扎复制梗阻性黄疸模型,假手术组(SO)仅麻醉、开腹而不结扎胆总管。BDL+anti-TNF-αMcAb治疗组于胆总管结扎第3天开始经尾静脉注射anti-TNF-αMcAb(1mg/kg),连用5d;BDL组和SO组以同样的方法注射等量的生理盐水。分别检测各组大鼠血清肌酐(Cr)、尿素氮(BUN)和TNF-α水平,并在光镜和电镜下观察各组大鼠肾组织的病理变化。结果 BDL组及BDL+anti-TNF-αMcAb组大鼠血清肌酐(Cr)、尿素氮(BUN)和TNF-α水平高于假手术组(SO),P<0.05。但BDL+anti-TNF-αMcAb组增高的程度低于BDL组(P<0.05),并且肾组织病理改变也较轻。SO组肾组织无明显病理改变。结论 TNF-α可能是梗阻性黄疸时肾损伤的重要介导因子,使用抗肿瘤坏死因子-α单克隆抗体,可以减轻实验鼠梗阻性黄疸时的肾损伤。

Objective To study the role of TNF-α in kidney injury with obstructive jaundice and the protective effect of anti-TNF-V McAb.Methods Twenty-four male Sprague-Dawley rats were randomly divided into bile duct-ligation（BDL） group,bile duct-ligation＋anti-TNF-α McAb（BDL＋anti-TNF-α McAb） group and sham-operation（SO） group.The model of obstructive jaundice was established in BDL group and BDL＋anti-TNF-α McAb group,SO group with only anesthetization and leparotomy but not bile duct-ligation.Group BDL＋anti-TNF-α McAb was subjected to injury with intravenous administration of anti-TNF-α McAb（1 mg/kg） respectively for five days,starting from the 3rd day after bile duct-ligation,BDL group and SO group followed by saline administration in the same manner.The levels of serum Cr,BUN and TNF-α were detected in each group.The histopathology were observed by light and electron microscopy in the model of kidney in rats with obstructive jaundice and in SO group rats.Results The levels of serum Cr,BUN and TNF-α in BDL group and BDL＋anti-TNF-α McAb group were markedly higher than those in SO group（P0.05）,and the levels of serum Cr,BUN and TNF-α in BDL＋anti-TNF-α McAb group were much lower than those in BDL group（P0.05）,the changes of kidney histopathology were minor in BDL＋anti-TNF-α McAb group.SO group had no obviously change.Conclusion TNF-α was an important mediator in kidney injury induced by obstructive jaundice,and the use of anti-TNF-α McAb can relieve the kidney injury.